MOTIVATION, BRAIN REWARD MECHANISMS AND BEHAVIOUR

1
MOTIVATION, BRAIN REWARD MECHANISMS AND BEHAVIOUR
2
What is Addiction?

• Addiction, dependence and abuse are often used
  interchangeably.
• Altman et al. (1996)
• Addiction is the extreme or psychopathological
  state where control over drug use is lost
• Dependence is the state of needing a drug to
  operate within normal limits
• Abuse is the use of drugs which leads to
  problems for the individual

3
Cocaine and Amphetamine

• Amphetamine
• inhibition of DA synthesis
• inhibition of MAO
• re-uptake blockade
• release of DA from vesicles

• Cocaine
• inhibition of DA synthesis
• re-uptake blockade
• release of DA from vesicles

4
The Rewarding Properties of Psychostimulants

• A number of methods are used to determine the
  reward pathways in the brain and the site of
  action of drugs
• Intra cranial self stimulation ICSS
• Drug self administration
• Conditioned place preference CPP

5
Mesolimbic DA A10 and Reward
6
Nicotine

• Obtained from tobacco
• ACh agonist

7
Nicotine and DA

• Imperato et al. (1986)
• nicotine increased DA in NAcc
• DOPAC and HVA

8
Theories of Addiction

• Positive reinforcement
• Negative reinforcement
• Sensitisation

9
Sensitisation

• Robinson Berridge (1993)
• Three major features of addiction
• 1. drug craving
• 2. persistence and reinstatement of drug craving
• 3. as craving increases (want) pleasure (liking)
  decreases

10
Sensitisation

• Common neural substrate mediates addiction
• this becomes sensitised
• Via conditioning drug-related stimuli start to
  control drug taking behaviour
• Sensitisation occurs to the wanting of the drug

11
Sensitisation
12
The Brain and Eating

• The hypothalamus
• A centre of feeding control
• A dual centre hypothesis
• a hunger centre
• a satiety centre
• Hypothesis generated from studies using rats

13
The Hypothalamus Neuroanatomy
14
The Lateral Hypothalamus

• Anand Brobeck (1951)
• bilateral electrolytic lesions of the LH
• stopped eating (aphagia)
• Teitelbaum Epstein (1962)
• aphagia accompanied by adipsia
• can recover some function if nursed intensively

15
The Ventromedial Hypothalamus

• Hetherington Ranson (1940)
• Bilateral electrolytic lesions of the VMH
• Hyperphagia (over eating)
• Two phases
• dynamic (immediately post-operative)
• static (enough to maintain obesity)

16
Lesions of the LH

• Lesions of the LH produce non-specific deficits
• Most notably deterioration of motor behaviour
• The hypothalamus is a region with both
• Intrinsic nuclei
• Fibres of passage (pass through without synaptic
  connection)

17
Is the Lesion of the LH Specific?

• It appears that the nigrostriatal (A9) pathway is
  also lesioned
• The substantia nigra to the striatum
• Dopamine (DA)
• This pathway is degenerated in Parkinsons disease

18
Neuropeptide Y (NPY) in LH

• Clark et al. (1984)
• Potent stimulator of food intake
• Flood Morley (1991) Jewitt et al. (1992)
• Neuropeptide Y in the LH
• Eat even in aversive conditions

19
NPY in the Hypothalamus

• Stanley et al. (1993)
• Midlateral hypothalamus
• Eating behaviour
• Paraventricular nucleus (PVN) (medial)
• Increases in insulin

20
Lesions of the VMH a reanalysis

• Lesions increase insulin levels
• VMH lesions increase lipogenesis
• body fat production
• VMH lesions decrease lipolysis
• breakdown of fat for utilization

21
Anatomical consequence of VMH lesions

• Axons destroyed that connect the PVN to the brain
  stem structures
• Ventral noradrenergic bundle

22
Lesions of PVN

• Gold et al. (1977) Leibowitz et al. (1981)
• Lesions of PVN or ventral noradrenergic bundle
• Hyperphagia